Leprosy is a chronic infectious disease afflicting millions of people worldwide. The overwhelming majority of leprosy cases occur in Third World countries. Approximately 3000 leprosy cases now exist in the United States and an average of 225 new cases are reported annually, almost all in recent immigrants from areas where leprosy is endemic.
The disease is caused by the obligate intracellular parasite Mycobacterium leprae (M. leprae), which is found in monocytes, macrophages, epithelial cells and, occasionally, peripheral nerve Schwann cells. The mechanism by which M. leprae is transmitted is as yet unknown and the time elapsing between infection with the organism and appearance of clinical symptoms can be as long as 10 years, during which time many others can unknowingly become infected.
Leprosy is a disease which presents a spectrum of diverse clinical and immunological manifestations. At one end of the spectrum are tuberculoid leprosy patients, who develop high levels of specific cell-mediated immunity, which ultimately kills and clears the bacilli in the tissues. Immunohistochemical studies have identified the predominant infiltrating lymphocytes as T4 helper cells. Peripheral nerve damage occurs concomitant with clearing of the bacilli in tuberculoid leprosy, and is thought to be immunologically mediated.
At the opposite end of the spectrum, lepromatous patients exhibit a selective unresponsiveness to antigens of M. leprae and the organisms often multiply to extraordinary numbers (e.g., 10.sup.10 /cm.sup.2 skin) Infiltrating lymphocytes are predominately of the T8 suppressor type. Peripheral nerve damage also occurs in lepromatous leprosy, although the mechanism of the damage is not clear. The majority of leprosy patients fall between these two extremes in the spectrum and are classified as borderline tuberculoid, borderline, or borderline lepromatous.
Because M. leprae attacks the nerve cells of the skin and peripheral nervous system, a loss of sensation and, in some cases, loss of control over muscles occurs in the extremities. As a result, leprosy victims often do not feel pain, and injuries to hands, arms, legs and feet are not noticed and frequently go untreated. Such wounds become infected; formation of scar tissue and scabs follows. Repeated injury results in gradual deformation and destruction of tissues.
A method of detecting the disease at an early stage would make it possible to screen populations in areas where the disease is common and begin treatment at an early stage in those affected, thus preventing nerve damage and deformity in the affected individual and limiting its transmission to others. Such a method is not available and diagnosis is presently delayed until clinical signs of the disease appear. Treatment of leprosy patients is not highly successful, particularly because M. leprae is becoming resistant to dapsone, the most widely used anti-leprosy drug. As many as 50 percent of new leprosy patients in some Asian clinics have drug-resistant leprosy.
As with other intracellular parasites, protective immunity against M. leprae is dependent on T cells and cell mediated immunity. Bloom, B. R. and T. Godal, Review of Infectious Diseases, 5:765-780 (1983). The human immune response to M. leprae has been shown to involve both T.sub.4 and T.sub.8 cells, which are thought to be involved in T cell help and T cell suppression, respectively. Little is known about the importance of individual M. leprae antigens for immune protection and/or suppression. It has been shown that T.sub.4 cells from sensitized individuals are stimulated in vitro by crude M. leprae protein preparations containing five of the most abundant polypeptides in M. leprae (e.g., five protein antigens which are 65 kD, 36 kD, 23 kD, 18 kD and 12 kD in molecular weight). In contrast, a pure phenolic glycolipid from M. leprae can activate human T.sub.8 cells to suppress a mitogenic response in vitro. Mehra, V. et al., Nature, 308:194 (1984).
At present, there is insufficient knowledge of leprosy and the causative organism, particularly in terms of an understanding of the contribution of the components of M. leprae to protective immunity. In addition, effective, specific and reliable means of diagnosing, preventing and controlling the disease are unavailable.